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Abstract

In a study of brainstem in the cynomolgus monkey, we found that the distribution of calbindin D28K (CB) and parvalbumin (PV) is nonoverlapping among functionally distinct sets of brainstem structures. Nuclei involved in representation and regulation of the organism's internal state contain CB, whereas those involved in the representation of the external environment and the representation or execution of externally directed actions contain only PV. Moreover, our findings indicate that different nuclei known as components of the ascending reticular activating system (ARAS) contain either CB or PV or both, suggesting that this system in primates operates with both CB and PV. In line with previously reported findings, we also found that unmyelinated pathways contain only CB, whereas myelinated pathways contain PV. Distribution of CB and PV in the macaque brainstem follows a pattern comparable to, but in some instances significantly different than, the pattern previously reported in the rat. We argue that the nonoverlapping distribution of CB and PV among different structures of the brainstem might reflect underlying differences in the physiological, anatomic, and perhaps phylogenetic properties of these structures. Considering our recent findings of selective vulnerability of brainstem structures to Alzheimer's disease, the present data suggest that the majority of macaque brainstem nuclei that contain CB are vulnerable to neurofibrillary tangles in humans. By contrast, only few nuclei that contain PV exhibit pathologic changes. Some of these nuclei are affected with a high number of neuritic plaques without ever developing neurofibrillary tangles.